What Is MTHFR and Should I Be Worried About It?

About two years ago, I went down the rabbit hole of genetic testing and discovered that I have a genetic mutation known as a homozygous MTHFR A1298C mutation. The homozygous part means that I have two copies of the mutation, one from each parent. MTHFR is the name of the gene itself, although when people say “I have MTHFR,” what they mean is that they possess one or two copies of its more damaging mutations. A1298C is the name of the variant of the gene that I possess. As I understand it, the variant gets its name because most people have an A at the 1,298th position in their MTHFR gene, I have a C. (Cytosine instead of Adenine. Along with Thymine and Guanine, these are the four nucleotides that make up all DNA. The building blocks of DNA could be a whole separate discussion, so I’ll leave it at this.)

There is another variant that can cause problems, the MTHFR C677T mutation, but as I do not have a copy of this in my DNA, I am not as knowledgeable about its effects. There is, however, much more research done about the C677T variant, which has more damaging effects on the body, so I hope that my focus on the A1298C variant will help spur interest in more research on this particular mutation.

What does the MTHFR gene do?

The U.S. National Library of Medicine explains that the full name of the MTHFR gene is methylenetetrahydrofolate reductase (NAD(P)H). Since that’s quite a mouthful, it’s more commonly referred to by its symbol, MTHFR. For those who have one of the MTHFR mutations mentioned above, you’ve probably already noticed that it looks like shorthand for a curse word that may feel appropriate to use when experiencing the gene’s effects on your body.

But when the gene is working properly, MTHFR is responsible for telling the body how to create the enzyme methylenetetrahydrofolate reductase. This enzyme is essential for the processing of folate, also known as vitamin B9, in the conversion of amino acids to create proteins and other compounds the body needs. One such compound is methylfolate, which is needed for both methylation and the BH4 cycle.

What does the BH4 cycle do?

The BH4 cycle does a few things, including helping break down phenylalanine and helping produce nitric oxide (NO). It also helps in the formation of several important neurotransmitters: melatonin, serotonin, dopamine, epinephrine, and norepinephrine.

What does methylation do?

Methylation is what happens when three hydrogens and a carbon (a methyl group) attach themselves to an enzyme, and methylfolate donates its methyl group to this process. This helps break down things like histamine and removes toxins from the body through the liver.

So what happens if you have an MTHFR mutation?

This is where the trouble starts. If you are homozygous for either the A1298C mutation or the C677T mutation, or if you have one copy of each mutation, your body has a greatly reduced capacity for breaking down the synthetic form of folic acid into its methylfolate form. While ingredient labels in the United States are allowed to use folate and folic acid interchangeably, they are not the same thing. Folic acid is an oxidized synthetic compound used in supplements and as a food additive. Folate is the term for various tetrahydrofolate derivatives that are naturally found in food.Natural folate gets metabolized in the small intestine, while folic acid has to go through the liver and requires dihydrofolate reductase in order to be metabolized. Folic acid metabolization wasn’t even a thing until the nutrient was first synthesized in 1943, and its consumption wasn’t widespread until the FDA mandated folic acid fortification in 1998 in an effort to combat neural tube defects.

While we can all agree that pregnant women should increase their intake of folate to decrease the risk of certain birth defects, supplementation for the masses has had unforeseen side effects – and they are not negligible. Most notably, high folic acid intake has been linked to an increase in certain types of cancer, including prostate cancer. For people with MTHFR mutations, folic acid intake can block the metabolization of natural folate, throwing a wrench into both methylation and the BH4 cycle.

What can you do if you have an MTHFR mutation?

(Obligatory I Am Not a Doctor disclosure. This should not be construed as medical advice. Please talk to a medical professional, particularly someone with knowledge of genetics, before making changes to your diet or starting any supplementation program.)

In my experience, my various doctors and specialists are completely unfamiliar with genetics-based medical advice, so I’ve had to take it upon myself to do research online and try to read the actual scientific studies whenever possible to sort out the sound advice from the pseudoscience. Your mileage may vary, but this is what I’ve gleaned for myself:

• Avoid consuming food items that have been fortified with synthetic folic acid. This is exceptionally difficult to do if you enjoy products made with wheat flour, as the FDA requires all-purpose flour to be fortified with folic acid. I look for products 100% whole wheat flour, but many brands also fortify whole grain products with folic acid, so be sure to look for it listed under Ingredients on the label. You cannot determine whether or not the folic acid content listed under Nutrition Facts is natural or synthetic, but if folic acid is not listed as an ingredient, it’s generally safe to assume that it is natural. Gluten-free products are another way to avoid all-purpose flour, but again, you need to check the ingredients to make sure the brand has not added folic acid anyway.
• Eat foods naturally rich in folate. Not all of these foods are palatable to me, but I will list them for your reference. Folate-rich foods include dark green vegetables, lentils, dried beans and peas, citrus fruits and juices, beets, strawberries, and tomatoes.
• Supplement with the bioavailable form of folate. It can be difficult to eat a sufficient amount of folate, especially when your body has had an insufficient amount of it for years, and supplementation is often beneficial. You do not want a multivitamin or a bottle labeled “folic acid.” You want to specifically find the supplements labeled as methylfolate, 5-MTHF, Metafolin, or Extrafolate-S. (I use Solgar folate 1000mcg.) Because of the way they work together, it can also be beneficial to supplement with the bioavailable form of vitamin B12, methylcobalamin. (I use Solgar sublingual methylcobalamin 1000mcg.) I cannot stress enough the importance of talking with your doctor about this. Even if your doctor is unfamiliar with this, it is good to let them know what you are trying in an effort to take back your health. There will be unpleasant side effects in the beginning.

Read my Big Fat Medical Update for more details.